β2-Microglobulin-Dependent Bacterial Clearance and Survival during Murine Klebsiella pneumoniae Bacteremia
β2-Microglobulin-Dependent Bacterial Clearance and Survival during Murine Klebsiella pneumoniae Bacteremia
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DOI：
10.1128/iai.00909-08
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Moore, Thomas A.
中科院分区：
文献类型：
--
作者：
Cogen, Anna L.;Moore, Thomas A.
肺炎克雷伯氏菌是社区获得性和医院获得性革兰氏阴性细菌肺炎的主要原因。克雷伯氏菌肺部感染的一个重要临床并发症是外周血播散，导致全身感染同时伴有局部肺部感染。我们在此报道了β 2-微球蛋白表达在小鼠K.肺炎菌血症。β（2）-微球蛋白敲除小鼠在静脉内接种后显示出显著增加的死亡率，这与血液、肝脏和脾脏中细菌负荷的增加相关。由于β 2-微球蛋白基因敲除小鼠缺乏CD 8 + T细胞和不变的NK T细胞，因此检查了两种细胞群体中特异性缺陷的小鼠模型，以观察这是否可以解释β 2-微球蛋白基因敲除小鼠中观察到的死亡率增加。令人惊讶的是，CD 8 T细胞缺陷（TAP-1敲除;体内抗CD 8抗体治疗）和不变NK（iNK）T细胞缺陷（CD 1d敲除，J α 281敲除）小鼠对K.肺炎菌血症。结合起来，这些研究清楚地表明β 2-微球蛋白依赖性但CD 8 T细胞和iNK T细胞非依赖性机制对K.肺炎菌血症。
Klebsiella pneumoniae is a leading cause of both community-acquired and nosocomial gram-negative bacterial pneumonia. A significant clinical complication of Klebsiella pulmonary infections is peripheral blood dissemination, resulting in a systemic infection concurrent with the localized pulmonary infection. We report here on the critical importance of beta(2)-microglobulin expression during murine K. pneumoniae bacteremia. beta(2)-Microglobulin knockout mice displayed significantly increased mortality upon intravenous inoculation that correlated with increased bacterial burden in the blood, liver, and spleen. As beta(2)-microglobulin knockout mice lack both CD8(+)T cells and invariant NK T cells, mouse models specifically deficient in either cell population were examined to see if this would account for the increased mortality noted in beta(2)-microglobulin knockout mice. Surprisingly, neither CD8 T-cell-deficient (TAP-1 knockout; in vivo anti-CD8 antibody treatment) nor invariant NK (iNK) T-cell-deficient (CD1d knockout, J alpha 281 knockout) mice were more susceptible to K. pneumoniae bacteremia. Combined, these studies clearly indicate the importance of a beta(2)-microglobulin-dependent but CD8 T-cell-and iNK T-cell-independent mechanism critical for survival during K. pneumoniae bacteremia.